The first classification criteria for IgG4-related disease have been finalised, creating greater clarity around this often elusive diagnostic entity. When compared against the gold standard of clinician diagnosis, the new classification criteria for IgG4-related disease had a sensitivity of 85.5% and a specificity of 99.2%. While not every patient diagnosed with IgG4-related disease would meet […]
The first classification criteria for IgG4-related disease have been finalised, creating greater clarity around this often elusive diagnostic entity.
When compared against the gold standard of clinician diagnosis, the new classification criteria for IgG4-related disease had a sensitivity of 85.5% and a specificity of 99.2%.
While not every patient diagnosed with IgG4-related disease would meet the formal criteria, the new classification boundaries were “quite robust” and would allow researchers to accurately identify patients for inclusion in clinical trials, Professor John Stone, the rheumatologist who led the development of the new criteria in collaboration with around 80 researchers across the globe, said.
The Classification Criteria for IgG4-Related Disease were announced at the ACR/ARHP Annual Meeting in Chicago in October, and are currently undergoing a review by ACR and EULAR.
The criteria have three steps. Firstly, to be classified as having IgG4-related disease a patient must present with a typical organ manifestation in any of the ten organs usually affected.
Then, a series of exclusion criteria apply.
“We found it important to ask, ‘What is this not?’ and exclude a number of these common mimickers,” Professor Stone, the director of clinical rheumatology at the Massachusetts General Hospital in Boston, said.
“Fever, for example, would be atypical of IgG4-related disease, lack of response to prednisone would be another.”
Finally, the researchers applied a complex inclusion criteria using a software called 1000Minds.
“The value of the approach we’ve taken is that it reflects very well what the clinician needs to do to make the diagnosis,” Professor Stone said.
“Clinicians have to integrate the clinical findings, the blood work, the radiologic findings and any pathology that is available. That’s how you approach the diagnosis. Any one of those alone is insufficient.”
IgG4-related is fiendishly difficult to diagnose. There is no single diagnostic test; only around two-thirds of patients have elevated serum IgG4 levels, and multiple organs are affected in 60-90% of patients.
“IgG4-related disease tends to present with mass lesions so one of the very common mistaken diagnoses is cancer,” Professor Stone said.
“I must have 20 patients who have undergone what is called a modified Whipple procedure because it was thought that they had pancreatic cancer.”
A modified Whipple is a surgical procedure in which part of the pancreas and duodenum is removed. People with IgG4-related disease who undergo this procedure unnecessarily are often left with diabetes mellitus and exocrine insufficiency as a result, which is why it’s “really, really important” that people with IgG4-related disease are not misdiagnosed, Professor Stone said.
IgG4-related disease can also mimic rheumatic diseases like Sjögren’s syndrome, granulomatosis with polyangiitis, giant cell arteritis and lupus. “But the treatment and the clinical considerations are different.”
The release of the classification criteria are an important milestone for IgG4-related disease, which was completely unknown only 15 years ago.
Elevated serum IgG4 was first described in 2001 by a group of Japanese investigators, and was associated with a disease called sclerosing pancreatitis.
“And then in 2003 investigators in Japan realised that patients with sclerosing pancreatitis not only had elevated IgG4 in their blood, they had identical pathological changes in a whole array of different organs, in the thyroid gland, in the major salivary gland, in the kidney, in the lung, indeed every organ in the body has been described as possibly being affected by what we now call IgG4-related disease,” Professor Stone said.
The literature gradually began to trickle to the west over the next five years, which was when Professor Stone diagnosed his first patient. The disease is now known to affect around 180,000 people in the US.
“I think it’s remarkable that an international group of investigators now have come together in only 15 years and developed a classification criteria,” Professor Stone said.
